The enzymatic activities of brain COMT and methionine sulfoxide reductase are correlated in a COMT Val/Met allele-dependent fashion
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Issue Date
2015-12Author
Moskovitz, Jackob
Walss-Bass, Consuelo
Cruz, Dianne A.
Thompson, Peter M.
Hairston, Jenaqua
Bortolato, Marco
Publisher
Wiley
Type
Article
Article Version
Scholarly/refereed, author accepted manuscript
Metadata
Show full item recordAbstract
AIMS: The enzyme catechol-O-methyl transferase (COMT) plays a primary role in the metabolism of catecholamine neurotransmitters and is implicated in the modulation of cognitive and emotional responses. The best-characterized single nucleotide polymorphism (SNP) of the COMT gene consists of a valine (Val)-to-methionine (Met) substitution at codon 108/158. The Met-containing variant confers a marked reduction in COMT catalytic activity. We recently showed that the activity of recombinant COMT is positively regulated by the enzyme Met sulfoxide reductase (MSR), which counters the oxidation of Met residues of proteins. The current study was designed to assess whether brain COMT activity may be correlated to MSR in an allele-dependent fashion. METHODS: COMT and MSR activities were measured from post-mortem samples of prefrontal cortices, striata and cerebella of 32 subjects, by using catechol and dabsyl-Met sulfoxide as substrates, respectively. Allelic discrimination of COMT Val108/185Met SNP was performed using the Taqman 5’nuclease assay. RESULTS: Our studies revealed that, in homozygous carriers of Met, but not Val alleles, the activity of COMT and MSR were significantly correlated throughout all tested brain regions. DISCUSSION: These results suggest that the reduced enzymatic activity of Met-containing COMT may be secondary to Met sulfoxidation, and point to MSR as a key molecular determinant for the modulation of COMT activity.
Description
This is the peer reviewed version of the following article: J. Moskovitz, C. Walss-Bass, D. A. Cruz, P. M. Thompson, J. Hairston and M. Bortolato (2015) Neuropathology and Applied Neurobiology The enzymatic activities of brain catechol-O-methyltransferase (COMT) and methionine sulphoxide reductase are correlated in a COMT Val/Met allele-dependent fashion, which has been published in final form at http://doi.org/10.1111/nan.12219. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.
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- Pharmacy Scholarly Works [293]
Citation
J. Moskovitz, C. Walss-Bass, D. A. Cruz, P. M. Thompson, J. Hairston and M. Bortolato (2015) Neuropathology and Applied Neurobiology The enzymatic activities of brain catechol-O-methyltransferase (COMT) and methionine sulphoxide reductase are correlated in a COMT Val/Met allele-dependent fashion
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